Dynamic ALFF Reveals Phase- and Network-Dependent Responses During Acute Severe Hypoxia

Abstract

Hypoxia constrains cerebral oxygen availability and challenges brain function. Previous work showed that functional connectivity reorganizes early during acute hypoxia, preceding cognitive deterioration, but the functional changes accompanying more severe hypoxic stress remain incompletely understood. We examined dynamic amplitude of low-frequency fluctuations (dALFF) in blood-oxygenation-level dependent (BOLD) fMRI during normoxia, sustained mild hypoxia, and transient severe hypoxia in healthy adults performing a continuous Go/No-go task with concurrent physiological monitoring. We characterized dALFF at whole-brain and network levels using a causal sliding-window approach, principal component analysis, and Schaefer's 17-network parcellation. Severe hypoxia elicited a non-monotonic, phase-dependent dALFF response that was not observed during normoxia or sustained mild hypoxia. Relative preservation during early hypoxia was followed by late-hypoxia suppression, which we operationally defined as a decompensation phase, and by a pronounced rebound after reoxygenation. Within this global response, dALFF became increasingly differentiated across intrinsic brain networks: DefaultA showed marked suppression, whereas SomMotB exhibited relative preservation or enhancement during decompensation. These changes were neither spatially uniform nor tightly synchronized with systemic oxygenation, while broadly overlapping temporally with cognitive deterioration. Together, these findings indicate that dALFF captures a complementary aspect of the brain's response to acute hypoxic stress, characterized by reversible, phase- and network-dependent reorganization of ongoing low-frequency BOLD dynamics under constrained oxygen availability.